title: The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function.
abstract: Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the integration of fibronectin and fibrinogen into a supportive intra-capsular matrix. Encapsulation maintained CSC viability under hypoxic stress conditions and, when compared to standard suspended CSC, media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, cardiac structure and function. Single cell encapsulation prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Canada K1Y4W7.
authors.forename: Audrey E
authors.initials: AE
authors.lastname: Mayfield
authors.forename: Everad L
authors.initials: EL
authors.lastname: Tilokee
authors.forename: Nicholas
authors.initials: N
authors.lastname: Latham
authors.forename: Brian
authors.initials: B
authors.lastname: McNeill
authors.forename: Bu-Khanh
authors.initials: BK
authors.lastname: Lam
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.forename: David W
authors.initials: DW
authors.lastname: Courtman
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
authors.forename: Darryl R
authors.initials: DR
authors.lastname: Davis
mesh_terms: D000368:Aged; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival; D017077:Culture Media, Conditioned; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D020100:Hydrogels; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D020100:Hydrogels
keywords: Cell therapy; Encapsulation; Heart failure; Myocardial infarction